Case Vignette

A 56-year-old school principal from Ilesa presents to the Surgical Oncology Clinic at OAUTHC with two months of weight loss, progressive jaundice, and upper abdominal pain radiating to the back. He also reports pale, bulky stools that float, and continued weight loss despite eating well.

CT scan shows a 3.4 cm mass in the head of the pancreas with 200° involvement of the superior mesenteric artery and 90° contact with the superior mesenteric vein, and no evidence of distant metastases. He undergoes ERCP and his bilirubin falls from 22 mg/dL to 2.5 mg/dL. Biopsy confirms pancreatic ductal adenocarcinoma.

Discussion Prompts

1. How would you stage this tumour according to the NCCN resectability criteria? Explain why upfront surgery is not recommended.
2. The patient has symptoms of pancreatic exocrine insufficiency. How would you prescribe pancreatic enzyme replacement therapy, and what counselling would you provide regarding its use and affordability?
3. Following biliary drainage, his bilirubin has fallen to 2.5 mg/dL. Would you recommend FOLFIRINOX or gemcitabine plus nab-paclitaxel? Justify your choice based on efficacy, toxicity, patient fitness, logistics, and cost.
4. His pain remains poorly controlled despite simple analgesics. Outline your approach to pain management, including the role of opioid analgesics and celiac plexus neurolysis.

1.     Staging and Resectability

By AJCC 8th edition this is cT4 N0/NX M0, Stage III. In AJCC 8, T4 is defined by arterial involvement (coeliac axis, SMA, or common hepatic artery) irrespective of size.

By NCCN resectability criteria this is unresectable, locally advanced pancreatic cancer (LAPC). The determining feature is the 200° SMA involvement, which exceeds the 180° threshold separating borderline resectable from unresectable disease. The 90° SMV contact is irrelevant to the decision in isolation, venous contact of that degree without contour irregularity would be resectable, but the arterial finding overrides it.

Why upfront surgery is not recommended

1.     R0 resection is not achievable. The SMA (retroperitoneal / uncinate) margin is already the commonest site of R1 positivity in a standard Whipple. With >180° circumferential involvement, the periadventitial plane is tumour-bearing along its whole dissected length. What you would deliver is an R1 or R2 resection.

2.     Margin-positive resection does not improve survival. Survival after R1/R2 resection approximates that of non-operative management, but with the added morbidity of pancreaticoduodenectomy. Even in high-volume centres, mortality is 2–5% and major morbidity 30–50%. Our figures are not better than that.

3.     The SMA is not reliably reconstructible. SMV/PV resection with reconstruction is standard practice and does not worsen outcome. Arterial resection is a different proposition, carrying substantially higher perioperative mortality with no demonstrated survival benefit outside highly selected series in specialized centres.

4.     Biology needs time to declare itself. Between 20% and 30% of patients with radiologically localized LAPC develop overt metastatic disease within the first few months of systemic therapy. Induction chemotherapy functions as a test of time and spares those patients a futile laparotomy. Hence a non-therapeutic laparotomy consumes a significant proportion of funds that the family has available for the whole of treatment.

5.     Post-operative attrition from adjuvant therapy. Up to half of patients never receive adjuvant chemotherapy after a Whipple because of complications or deconditioning. Giving systemic therapy first guarantees delivery of the component of treatment which drives survival.

Correct pathway

With the above investigation done, an initial Ca 19:9 is required → induction systemic chemotherapy → restaging at 8–16 weeks with pancreatic-protocol triphasic CT plus Ca 19:9 → consideration of consolidative chemoradiation or SBRT in non-progressors →surgical exploration only in the minority with a convincing response.

2.     Pancreatic Enzyme Replacement Therapy

Diagnosis: steatorrhoea with weight loss despite adequate intake is sufficient grounds to treat. Faecal elastase-1 (<200 µg/g abnormal, <100 severe) confirms it but is unavailable to us in most cases, and the diagnosis here is clinical. You can begin treatment irrespective.

Prescription

•     40,000–50,000 units of lipase with each main meal, and half that with snacks.

•     Titrate up to 75,000–80,000 units per meal if steatorrhoea persists.

•     Take with the first mouthfuls and distributed through the meal — not before, not after.

•     Swallow whole. Enteric-coated microspheres must not be crushed or chewed, and must not be taken with hot drinks.

•     If response is inadequate at an adequate dose, add a PPI (omeprazole 20–40 mg daily). Pancreatic bicarbonate secretion is also lost, so duodenal pH is low enough to inactivate the enzyme before it can act.

Counselling that actually matters locally

Count units, not capsules

This is the single commonest error I see. Creon is available in 10,000, 25,000 and 40,000 unit strengths, and generic “pancreatin” tablets sold in patent medicine shops often contain a small fraction of that and are not enteric-coated. A patient taking two low-dose pancreatin tablets is functionally untreated. Write the prescription in lipase units per meal, and tell him explicitly what to check on the box.

Cost

At 40,000 units per meal, he needs one 40,000 capsule or two 25,000 capsules per meal, three meals a day. Explain the monthly cost up front rather than letting him discover it at the pharmacy and quietly stop. Practical mitigations: use the highest available strength to reduce cost per unit and pill burden; prioritize full dosing at main meals if he must ration; buy in bulk where the pharmacy allows; and involve the family early, because this is a recurring cost that will run alongside chemotherapy for the rest of his life.

Do not restrict fat as it worsens the calorie deficit and deepens fat-soluble vitamin deficiency. The correct approach is enough enzyme to permit a normal fat intake, with small, frequent, energy-dense meals.

Adjuvant supplement vitamins A, D, E and K is important and screen for pancreatogenic (type 3c) diabetes with a fasting glucose or HbA1c as it is present in a large proportion of these patients and will complicate his nutrition and his steroid use.

Manage patient expectations. As stools should firm up and lose their oiliness within a week; weight stabilizes over time. Tell him he must take it with every meal, permanently, and that feeling better is not a reason to stop.

3.     FOLFIRINOX versus Gemcitabine + Nab-Paclitaxel

Neither of the agents is advised to be given at the current serum levels. Ideally you must monitor the bilirubin levels for about 10 days and confirm that its declining and be sure that the stent is patent. And if a molecule must be given, single agent Gemcitabine is preferable. However between Irinotecan and Gemcitabine + Nab-Paclitaxel, FOLFORINOX has the risk of severe neutropenia and diarrhoea is substantially increased, and full-dose irinotecan within a combination regimen may not be appropriate and Nab-paclitaxel is not recommended in pancreatic adenocarcinoma at a bilirubin above approximately 1.25 × ULN. But once bilirubin normalizes FOLFORINOX is a better option. Below shows a comparism between the 2 agents.

Hence I recommendation

Modified FOLFIRINOX, assuming ECOG 0–1 and a normalised bilirubin.

•     He is 56, a working professional, and the LAPC data supporting FOLFIRINOX are considerably stronger. If there is any prospect of conversion to resection, this is the regimen that delivers it.

•     Cost favours FOLFIRINOX in Nigeria, which surprises trainees. Oxaliplatin, irinotecan, 5-FU and folinic acid are all off-patent and locally obtainable. Nab-paclitaxel is expensive, frequently out of stock, and has no substitute. Conventional paclitaxel is a different drug with different pharmacology and is not evidence-based here — do not let anyone make that swap.

•     Ilesa to Ile-Ife is a short journey. Two-weekly attendance is realistic for him in a way it would not be for a patient from Sokoto. Note also that gemcitabine/nab-paclitaxel actually demands more visits (three of every four weeks), so the travel argument runs the opposite way from what fellows usually assume.

4.     Pain Management

First, you need to define where the pain is coming from. It can either be from the tumour or from the physiologic processes surrounding the tumour which could either be stent occlusion or early cholangitis, gastric outlet obstruction, or simply untreated exocrine insufficiency producing cramping and bloating. If these causes are excluded, then you can now treat what is a mixed visceral and neuropathic pain. The pain radiating to the back shows retroperitoneal extension and perineural invasion along the coeliac and splanchnic plexuses — a defining feature of pancreatic adenocarcinoma.

It is usually advisable to follow the pain ladder.

1.     Paracetamol 1g qds as the standing base. NSAIDs with caution, given his nutritional state and bleeding risk.

2.     Avoid weak as it may not help this degree of pain hence do not waste weeks on it.

3.     Oral morphine. Start immediate-release 5 mg every 4 hours, with a breakthrough dose of one-sixth of the total daily dose available as often as hourly. Titrate up by 30–50% every 24–48 hours against the number of breakthrough doses used. Always co-prescribe a stimulant laxative (senna or bisacodyl), regularly rather than as required. Constipation is the reason patients stop morphine. Add metoclopramide 10 mg tds for the first week.

4.     Adjuvants: Tabs amitriptyline 10–25 mg nocte for the neuropathic component — cheap and widely available; gabapentin if amitriptyline is not tolerated. Dexamethasone 4–8 mg daily helps retroperitoneal neural compression and also appetite, but watch his glucose given the likelihood of type 3c diabetes.

Coeliac Plexus Neurolysis

Rationale

Chemical destruction of the coeliac plexus interrupts visceral afferent transmission from the pancreas and upper abdominal viscera. Absolute alcohol (50–98%) is used after a local anaesthetic test dose.

Approaches, in order of local feasibility

•     Intraoperative chemical splanchnicectomy. If he is undergoing staging laparoscopy, do it at the same sitting. It is cheap and quick, and Lillemoe’s randomised data showed improved pain scores in patients with pre-operative pain. In our setting this is the most reliably deliverable option, and it is routinely missed.

•     Percutaneous CT- or fluoroscopy-guided posterior block, where interventional radiology is available.

•     EUS-guided anterior neurolysis is the safest and most precise, but EUS access is the limiting factor.

Complications to consent for

Transient hypotension from sympathetic blockade (pre-hydrate), transient diarrhoea from unopposed parasympathetic activity, and a local pain flare. Rare but serious: retroperitoneal haemorrhage and, very rarely, paraplegia from anterior spinal artery injury.